This research is concerned primarily with improving old and developing new techniques applicable to the treatment of human malignancies by modalities including radiotherapy. It involves model studies on three levels: computer simulation; cultures of density inhibited Chinese hamster cells; and a transplantable mammary sarcoma (EMT-6) in vivo. Specific areas to be investigated include: Repair of potentially lethal lesions after radio-chemotherapy; effects of elevated temperatures, during and after radio-chemotherapy, on cell survival and repair; the investigation, by immunological techniques, of the specific lesions introduced into the DNA by various modalities (particularly by X-irradiation) and their repair; the application of previously developed mathematical techniques to aid in developing new strategies for radio-chemotherapy. To achieve our goals we will utilize standard tissue culture techniques; methods of tumor radiobiology involving in vivo experiments coupled with tissue culture assays; computer simulations of radio-chemotherapy projects. The investigation of specific DNA lesions will utilize the development of anti-sera against specific types of damage and fluorescent techniques to determine antibody binding to the DNA. BIBLIOGRAPHIC REFERENCES: G.M. Hahn, Radiotherapy and chemotherapy: parallels and differences. Radiology 114, 203-211 (1975). G.M. Hahn, J. Braun, and I. Har-Kedar, Thermochemotherapy: Synergism between hyperthermia (42-43 degrees C) and adriamycin (or bleomycin) in mammalian cell inactivation. Proc. Natl. Acad. Sci. USA 72, 937-940 (1975).